Structural Diversity of Ethinyl Estradiol Solvates

Structural Diversity of Ethinyl Estradiol Solvates Crystal Growth & Design, Vol. 8, No. 3, 2008 831
of the hemihydrate, the methanolate, and ACN solvates were
also redetermined from single-crystal XRPD data. An attempt
to determine the crystal structure of the toluene solvate failed
because of the instability of the crystallized material.
The characteristic H-bonds formed by the ethinyl estradiol
pseudo-polymorphs are between the -OH groups attached to
C(3) and/or C(17) and the corresponding solvent molecules, as
well as H-bonds between different ethinyl estradiol molecules,
namely, between the -OH groups attached to C(3) and those
attached to C(17). Ethinyl estradiol forms pseudo-polymorphs
mainly with solvents having H-bond accepting or both accepting
and donating propensity and shows a remarkable flexibility in
forming distinctly different H-bonding patterns, resulting in a
diverse set of solvate structures. A high degree of similarity
can be observed between the crystal packing of the nitromethane
and dioxane solvates, forming isostructural sheets of ethinyl
estradiol molecules arranged parallel in a head-to-tail fashion.
DSC and hot-stage XRPD measurements showed that, upon
heating, all the ethinyl estradiol pseudo-polymorphs convert to
the anhydrate form before melting.
Acknowledgment. This research was supported by the
Technology Foundation STW, the Applied Science Division of
NWO, and the Technology Program of the Ministry of
Economic Affairs.
Supporting Information Available: X-ray crystallographic information
files (CIF) are available for all the investigated structures. This
material is available free of charge via the Internet at http://pubs.acs.org.
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